A 12-year-old boy has recurrent stroke-like episodes, lactic acidosis, and episodic vomiting. Muscle biopsy shows ragged red fibers on modified Gomori trichrome stain. His mother had similar episodes; his father is asymptomatic and none of his siblings via the father are affected. Which property of mitochondrial inheritance best explains this pattern?

• A All mitochondria of an offspring derive from the ovum, and variable heteroplasmy modifies expression ✓
• B Mitochondrial genes undergo genomic imprinting according to parental origin
• C Sperm contribute mitochondria that are selectively activated after fertilization
• D mtDNA replicates independently of cell division, so all offspring inherit identical mutant loads

Explanation

Mitochondrial DNA is transmitted exclusively through the mother because the ovum supplies essentially all mitochondria to the embryo; paternal mitochondria in sperm do not contribute meaningfully. Affected mothers pass the mutation to all children, but the proportion of mutant versus wild-type mtDNA molecules, called heteroplasmy, varies among tissues and among siblings, producing variable severity and threshold effects. Ragged red fibers reflect subsarcolemmal mitochondrial proliferation, characteristic of MELAS.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.